Is DAPK2 p.Thr142Pro (c.424A>C) pathogenic?

DAPK2 p.Thr142Pro (c.424A>C) is classified Uncertain significance in DAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.8508); Ultra-rare (popmax 0.07%, amr).

How common is DAPK2 p.Thr142Pro (c.424A>C) in the general population?

DAPK2 p.Thr142Pro (c.424A>C) is ultra-rare (popmax 0.07%, amr) (gnomAD).

What do computational predictors say about DAPK2 p.Thr142Pro (c.424A>C)?

AlphaMissense predicts likely pathogenic (score 0.8508) — an in-silico prediction, not a clinical call.

DAPK2 p.Thr142Pro

c.424A>C · rs555303465 · VCV2355239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8508	likely pathogenic
REVEL	0.071	moderately benign-leaning
SaProt	LLR -12.99	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	GERP -0.36, phastCons 0.34
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.07% Admixed American · 42/60,030 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0473%

Overall 0.00533% 86/1,614,232 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.07%	1,429
European (non-Finnish)	0.00364%	27,443
Remaining individualsnot grpmax-eligible	0.0016%	62,512

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DAPK2
Protein: p.Thr142Pro
Coding: c.424A>C
MANE Select: NM_014326
dbSNP: rs555303465
Type: single nucleotide variant
Location: chr15:63971452 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 11 PDB
Residue 142: the protein kinase domain; an α-helix

Full DAPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPK2 c.632+8G>T Benign/Likely benign ★★ same type
DAPK2 p.Arg60= Likely benign ★★ same type
DAPK2 p.Arg60Gln Likely benign ★★ ⚠ same type
DAPK2 p.Arg68Gln Benign/Likely benign ★★ ⚠ same type
DAPK2 p.Thr270= Benign ★★ same type
DAPK2 p.Ala126Val Uncertain significance ★ ⚠ same type
DAPK2 p.Ala175Pro Uncertain significance ★ ⚠ same type
DAPK2 p.Ala175Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dapk2-p-thr142pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown